title: Phage display identification of CD100 in human atherosclerotic plaque macrophages and foam cells.
abstract: Atherosclerosis is a complex disease in which vessels develop plaques comprising dysfunctional endothelium, monocyte derived lipid laden foam cells and activated lymphocytes. Considering that humans and animal models of the disease develop quite distinct plaques, we used human plaques to search for proteins that could be used as markers of human atheromas. Phage display peptide libraries were probed to fresh human carotid plaques, and a bound phage homologous to plexin B1, a high affinity receptor for CD100, was identified. CD100 is a member of the semaphorin family expressed by most hematopoietic cells and particularly by activated T cells. CD100 expression was analyzed in human plaques and normal samples. CD100 mRNA and protein were analyzed in cultured monocytes, macrophages and foam cells. The effects of CD100 in oxLDL-induced foam cell formation and in CD36 mRNA abundance were evaluated. Human atherosclerotic plaques showed strong labeling of CD100/SEMA4D. CD100 expression was further demonstrated in peripheral blood monocytes and in in vitro differentiated macrophages and foam cells, with diminished CD100 transcript along the differentiation of these cells. Incubation of macrophages with CD100 led to a reduction in oxLDL-induced foam cell formation probably through a decrease of CD36 expression, suggesting for the first time an atheroprotective role for CD100 in the human disease. Given its differential expression in the numerous foam cells and macrophages of the plaques and its capacity to decrease oxLDL engulfment by macrophages we propose that CD100 may have a role in atherosclerotic plaque development, and may possibly be employed in targeted treatments of these atheromas.
authors.affiliation: Heart Institute of São Paulo (InCor), HC-FMUSP, São Paulo, São Paulo, Brazil ; Clinical Immunology and Allergy, Department of Clinical Medicine, University of São Paulo Medical School - HC-FMUSP, São Paulo, São Paulo, Brazil.
authors.forename: Maria Carolina Aquino
authors.initials: MC
authors.lastname: Luque
authors.forename: Paulo Sampaio
authors.initials: PS
authors.lastname: Gutierrez
authors.forename: Victor
authors.initials: V
authors.lastname: Debbas
authors.forename: Waleska Kerllen
authors.initials: WK
authors.lastname: Martins
authors.forename: Pedro
authors.initials: P
authors.lastname: Puech-Leao
authors.forename: Georgia
authors.initials: G
authors.lastname: Porto
authors.forename: Verônica
authors.initials: V
authors.lastname: Coelho
authors.forename: Laurence
authors.initials: L
authors.lastname: Boumsell
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Beatriz
authors.initials: B
authors.lastname: Stolf
mesh_terms: D000704:Analysis of Variance; D015703:Antigens, CD / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D018955:CD36 Antigens / Q000378:metabolism; D061505:Cell Surface Display Techniques; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000737:chemistry* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D039961:Semaphorins / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C093224:CD100 antigen; D018955:CD36 Antigens; D017931:DNA Primers; D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D039961:Semaphorins